It is the objective of this proposal to investigate the biochemical mechanisms of acrylamide neurotoxicity. Acrylamide inhibits total rat brain enolase activity in vitro. When given chronically, however, it only inhibits an isoenzyme of enolase (neuron specific enolase, NSE) both in peripheral nerve and brain of rats. NSE can be separated from other enolase enzymes by ion exchange chromatography and by differential heat stability. Studies to show a causal relationship between acrylamide inhibition of NSE and neurotoxicity will include determining the acute effects of acrylamide administration in NSE and determining NSE activity during the onset of neurotoxicity and during recovery from the neuropathy in rat brain and sciatic nerve. Similarly, the NSE activity of cat sciatic nerve will be studied at several cumulative doses of acrylamide. In order to evaluate the selectivity of acrylamide for NSE, in vivo its uptake will be studied in glial- and neuron-enriched fractions from rat brain. The interaction of acrylamide with NSE will be studied in terms of kinetics and sulfhydryl group binding. The effect of non-neurotoxic and neurotoxic analogs of acrylamide on NSE will be evaluated as well as the effect of other neurotoxic compounds such as 2,5-hexanedione and isoniazed. Additionally, the effect of acrylamide on other enzymes of glycolysis will be studied including phosphofructokinase, glyceraldehyde 3-phosphate dehydrogenase and lactic dehydrogenase.